High mobility group box 1 mediates inflammatory responses in malignant peritoneal mesothelioma.

BACKGROUND: Serum high mobility group box 1 (HMGB1) serves as a diagnostic biomarker for malignant peritoneal mesothelioma (MPM) patients, yet its diagnostic significance within MPM tumor tissues remains uncertain. This study aims to elucidate the roles of HMGB1 in MPM. METHODS: HMGB1 expression analysis was conducted in both tumor and adjacent non-cancerous tissues collected from MPM patients. The two-year follow-up of MPM patients commenced from the diagnosis date. Inflammatory cytokine analysis was performed on these tissues, and Pearson correlation coefficient analysis was applied to examine variable relationships. In vitro assays included constructing an HMGB1 knockdown cell line, assessing cell viability, apoptosis, and inflammatory cytokine levels to delineate HMGB1's roles in MPM. RESULTS: HMGB1 overexpression was observed in MPM tumor tissues, particularly in stages III-IV. Diagnostic implications of HMGB1 for MPM were evident, augmenting its diagnostic value. HMGB1 overexpression correlated with diminished survival rates. Positive correlations existed between inflammatory cytokines and HMGB1 in MPM tumor tissues and cell lines. Suppression of HMGB1 regulated cell growth and apoptosis in MPM cell lines. CONCLUSION: HMGB1 exhibits diagnostic potential for MPM and modulates inflammatory responses within the disease context.

Recurrent patellar dislocation patients with high-grade J-sign have multiple structural bone abnormalities in the lower limbs.

PURPOSE: To explore the relationship between preoperative J-sign grading and structural bone abnormalities in patients with recurrent patellar dislocation (RPD). METHODS: A retrospective study was conducted on RPD patients over 5 years. Patients were categorised based on J-sign grade into low (J- and J1+), moderate (J2+) and high groups (J3+). Trochlear dysplasia (TD) and osseous structures (femoral anteversion angle [FAA], knee torsion, tibial tuberosity-trochlear groove [TT-TG] distance, Caton-Deschamps index) were assessed and grouped according to risk factor thresholds. The χ2 test was used to compare composition ratio differences of structural bone abnormalities among the groups. RESULTS: A total of 256 patients were included, with 206 (80.5%) females. The distribution of J-sign grade was as follows: 89 knees (34.8%) of low grade, 86 moderate (33.6%) and 81 high (31.6%). Among the five structural bone abnormalities, TD was the most common with a prevalence of 78.5%, followed by increased TT-TG at 47.4%. Excessive tibiofemoral rotation had the lowest occurrence at 28.9%. There were 173 (67.6%) patients who had two or more abnormalities, while 45 (17.6%) had four to five bony abnormalities. Among patients with any bony abnormality, the proportion of high-grade J-sign surpassed 40%. Patients with moderate and high-grade J-sign had more increased FAA and more pronounced patella alta (all p < 0.001). The proportion of excessive knee torsion and TD increased with increasing each J-sign grade, with the more notable tendency in knee torsion (high vs. moderate vs. low-grade: 61% vs. 22% vs 7%, p < 0.001). Furthermore, the higher J-sign grade was also associated with more combined bony abnormalities (p < 0.001). In the high-grade J-sign group, 90.2% of the knees had two or more bony risk factors and 40.7% had four or more, which were significantly higher than the moderate and low-grade J-sign groups (40.7% vs. 11.6% vs. 2.2%, p < 0.001). CONCLUSION: In patients with a high-grade J-sign, over 90% of the lower limbs had two or more structural bone risk factors, and more than 40% had four or more. These proportions were significantly higher compared to knees with low-grade and moderate J-sign. In clinical practice, when treating high-grade patellar mal-tracking, it is important to focus on and correct these strongly correlated abnormal bone structures. LEVEL OF EVIDENCE: Level III.

Mechanisms of electroacupuncture relieves uterine smooth muscle spasm in dysmenorrhea rats based on Rho/ROCK signaling pathway. / 基于Rho/ROCKä¿¡å·é€šè·¯æŽ¢è®¨ç”µé’ˆä»»è„‰ã€ç£è„‰ç»ç©´ç¼“è§£ç±»ç—›ç»æ¨¡åž‹å¤§é¼ å­å®«å¹³æ»‘è‚Œç—‰æŒ›çš„æœºåˆ¶.

OBJECTIVES: To investigate the effect of electroacupuncture (EA) on Rho/Rho-associated coiled-coil-forming kinases (ROCK) signaling pathway of uterus tissue in rats with dysmenorrhea, so as to explore the underlying mechanism of EA treating primary dysmenorrhea (PD) and uterine smooth muscle spasm, and to observe whether there is a difference in the effect of meridian acupoints in Conception Vessel (CV) and Governer Vessel (GV). METHODS: Sixty female SD rats were randomly divided into saline, model, CV, GV, and non-acupoint groups, with 12 rats in each group. The dysmenorrhea model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin (OT). EA (2 Hz) was applied to "Qihai" (CV6) and "Zhongji" (CV3) for CV group, "Mingmen" (GV4) and "Yaoshu" (GV2) for GV group, "non-acupoint 1" and "non-acupoint 3" on the left side for non-acupoint group, and manual acupuncture was applied to "Guanyuan" (CV4) for CV group, "Yaoyangguan" (GV3) for GV group, "non-acupoint 2" on the left side for non-acupoint group. The treatment was conducted for 20 min each time, once daily for 10 days. The writhing score was evaluated. The smooth myoelectric signals of rats' uterus in vivo were recorded by multi-channel physiological recorder. The uterine histopathological changes were observed by HE staining. The contents of prostaglandin F2α (PGF2α), OT and calcium ion (Ca2+) in uterine tissue of rats were detected by ELISA. The protein and mRNA expression levels of smooth muscle 22-α (SM22-α), RhoA and ROCKⅡ in uterine tissue were detected by Western blot and fluorescence quantitative PCR, respectively. RESULTS: Compared with the saline group, the writhing score of rats in the model group was increased (P<0.01), the amplitude voltage of uterine smooth muscle in vivo was elevated (P<0.01), the contents of PGF2α, OT and Ca2+, the protein and mRNA expression of SM22-α, RhoA and ROCK Ⅱ in uterine tissue were all increased (P<0.01). Compared with the model and the non-acupoint groups, the writhing scores of the CV and the GV groups were decreased (P<0.01, P<0.05), the amplitude voltage of uterine smooth muscle was decreased (P<0.01), the contents of PGF2α, OT and Ca2+ in uterine tissue were decreased (P<0.01, P<0.05), and the protein expression and mRNA expression of SM22-α, RhoA and ROCKⅡ in uterine tissue were decreased (P<0.01, P<0.05). HE staining showed extensive exfoliation of uterine intima with severe edema and increased glandular secretion in the model group, which was alleviated in the CV and GV groups. CONCLUSIONS: EA at acupoints of CV and GV can significantly reduce the writhing score, uterine smooth muscle amplitude voltage, pathological injury degree of uterus, and relieve spasm of uterine smooth muscle in dysmenorrhea rats, which may be related to its effect in regulating PGF2α and OT contents, inhibiting the Rho/ROCK signaling pathway, and reducing the SM22-α, RhoA, ROCKⅡ protein and mRNA expression, and Ca2+ content in uterine tissue.

scNovel: a scalable deep learning-based network for novel rare cell discovery in single-cell transcriptomics.

Single-cell RNA sequencing has achieved massive success in biological research fields. Discovering novel cell types from single-cell transcriptomics has been demonstrated to be essential in the field of biomedicine, yet is time-consuming and needs prior knowledge. With the unprecedented boom in cell atlases, auto-annotation tools have become more prevalent due to their speed, accuracy and user-friendly features. However, existing tools have mostly focused on general cell-type annotation and have not adequately addressed the challenge of discovering novel rare cell types. In this work, we introduce scNovel, a powerful deep learning-based neural network that specifically focuses on novel rare cell discovery. By testing our model on diverse datasets with different scales, protocols and degrees of imbalance, we demonstrate that scNovel significantly outperforms previous state-of-the-art novel cell detection models, reaching the most AUROC performance(the only one method whose averaged AUROC results are above 94%, up to 16.26% more comparing to the second-best method). We validate scNovel's performance on a million-scale dataset to illustrate the scalability of scNovel further. Applying scNovel on a clinical COVID-19 dataset, three potential novel subtypes of Macrophages are identified, where the COVID-related differential genes are also detected to have consistent expression patterns through deeper analysis. We believe that our proposed pipeline will be an important tool for high-throughput clinical data in a wide range of applications.

Construction and validation of chronic pain prediction model after total knee arthroplasty.

Objective: To explore the risk factors of chronic pain after total knee arthroplasty (TKA) and to establish and verify a prediction model. Methods: As a retrospective observational study, medical records of 239 patients who underwent TKA in Affiliated Hospital of Jiangnan University from January 2020 to December 2022 were reviewed. Fifty four patients suffered from chronic pain after TKA surgery. Univariate and multivariate logistic regression were used to analyze factors associated with the occurrence of chronic pain after TKA. A nomogram prediction model was established based on the identified independent risk factors, and its predictive effectiveness was evaluated. Results: Gender, postoperative 24-hourss numerical rating scale (NRS) and postoperative three months Hospital for Special Surgery Knee-Rating (HSS) scores were independent risk factors for chronic pain after TKA (p<0.05). The area of the receiver operating characteristic (ROC) of the nomogram model based on these factors was 0.904 (95% confidence interval [CI): 0.861-0.947), which indicates a good predictive value for the postoperative chronic pain. When the optimal cut off value was selected, the sensitivity and specificity of the model were 92.6% and 74.1%, respectively, indicating that the predictive model is effective. Conclusions: Gender, postoperative 24-hours NRS and postoperative three months HSS score are independent risk factors for chronic pain after TKA. The nomogram prediction model based on these factors is effective and can provide auxiliary reference for patients with chronic pain after TKA.

Effectiveness and safety of auricular acupuncture on adjuvant analgesia in patients with total knee arthroplasty: a randomized sham-controlled trial.

Objective: This study aimed to evaluate the effectiveness and safety of auricular acupuncture (AA) on postoperative analgesia, the degree of postoperative nausea, and the effect of inflammation after total knee arthroplasty (TKA). Methods: This was a single-center, placebo-controlled, randomized clinical trial. In total, 96 patients were randomly divided into an AA group with an indwelling intradermal needle (n = 48) and a sham auricular acupuncture (SAA) group with a non-penetrating placebo needle (n = 48). Intra-spinal anesthesia was adopted in both groups during surgery, and an epidural analgesic pump was implanted after surgery for 48 h. The primary outcome was the post-surgery visual analog score (VAS) of resting and movement states (at 6, 12 h and 1, 2, 3, 5, and 7 days). The secondary outcomes included additional doses of analgesic injection during the treatment, C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count on the 1st, 3rd, and 7th day after the operation, nausea on the 1st, 2nd, and 3rd day after the operation, the Hospital for Special Surgery Knee Score (HSS) on the 2nd and 12th week after the operation, and adverse events. Results: The VAS in the AA group at 6 h, 12 h, 2, 3, and 5 days after surgery were lower than those of the SAA group (p < 0.05). Among the secondary outcomes, the total dose of additional analgesic injection after surgery in the AA group was lower than that in the SAA group (p < 0.05). The serum CRP on the 1st day after operation in the AA group was lower than that in the SAA group (p < 0.05). The degree of nausea on 2nd day after surgery in the AA group was lower than that in the SAA group (p < 0.05). There was no significant difference in other outcomes (p > 0.05). Conclusion: In this study, AA was shown to be an effective and safe complementary and alternative therapy for pain relief after TKA, which was able to reduce the total postoperative dose of additional painkillers, decrease serum CRP 1 day after surgery, and improve the degree of postoperative nausea. Clinical trial registration: www.chictr.org.cn, ChiCTR2100054403.

A photo-degradable BODIPY-modified Ru(II) photosensitizer for safe and efficient PDT under both normoxic and hypoxic conditions.

Photodynamic therapy (PDT) is promising for cancer treatment but still suffers from some limitations. For instance, PDT based on 1O2 generation (in a type-II mechanism) is heavily dependent on high oxygen concentrations and will be significantly depressed in hypoxic tumors. In addition, the residual photosensitizers after PDT treatment may cause severe side-effects under light irradiation. To solve these problems, herein a BODIPY (boron dipyrromethene)-modified Ru(II) complex [Ru(dip)2(tpy-BODIPY)]2+ (complex 1, dip = 4,7-diphenyl-1,10-phenanthroline, tpy = 2,2':6',2''-terpyridine) was designed and synthesized. Complex 1 exhibited both high singlet oxygen quantum yield (Φ = 0.7 in CH3CN) and excellent superoxide radical (O2˙-) generation, and thus demonstrated efficient PDT activity under both normoxic and hypoxic conditions. Moreover, complex 1 is photo-degradable in water, and greatly loses its ROS generation ability after PDT treatment. These novel properties of complex 1 make it promising for efficient PDT under both normoxic and hypoxic conditions with reduced side-effects.

Non-alcoholic fatty liver disease promotes liver metastasis of colorectal cancer via fatty acid synthase dependent EGFR palmitoylation.

Liver metastasis is the major reason for most of colorectal cancer (CRC) related deaths. Accumulating evidence indicates that CRC patients with non-alcoholic fatty liver disease (NAFLD) are at a greater risk of developing liver metastasis. With the growing prevalence of NAFLD, a better understanding of the molecular mechanism in NAFLD-driven CRC liver metastasis is needed. In this study, we demonstrated that NAFLD facilitated CRC liver metastasis as a metabolic disorder and promoted the stemness of metastatic CRC cells for their colonization and outgrowth in hepatic niches. Metabolically, the lipid-rich microenvironment in NAFLD activated de novo palmitate biosynthesis in metastatic CRC cells via upregulating fatty acid synthase (FASN). Moreover, increased intracellular palmitate bioavailability promoted EGFR palmitoylation to enhance its protein stability and plasma membrane localization. Furthermore, we demonstrated that the FDA-approved FASN inhibitor orlistat could reduce NAFLD-activated endogenous palmitate production, thus inhibiting palmitoylation of EGFR to suppress CRC cell stemness and restrict liver metastasis in synergy with conventional chemotherapy. These findings reveal that the NAFLD metabolic microenvironment boosts endogenous palmitate biosynthesis in metastatic CRC cells and promotes cell stemness via EGFR palmitoylation, and FASN inhibitor orlistat could be a candidate adjuvant drug to suppress liver metastasis in CRC patients with NAFLD.

Efficacy and safety of mesenchymal stem cell therapy in liver cirrhosis: a systematic review and meta-analysis.

AIM: Although the efficacy and safety of mesenchymal stem cell therapy for liver cirrhosis have been demonstrated in several studies. Clinical cases of mesenchymal stem cell therapy for patients with liver cirrhosis are limited and these studies lack the consistency of treatment effects. This article aimed to systematically investigate the efficacy and safety of mesenchymal stem cells in the treatment of liver cirrhosis. METHOD: The data source included PubMed/Medline, Web of Science, EMBASE, and Cochrane Library, from inception to May 2023. Literature was screened by the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Outcome indicators of the assessment included liver functions and adverse events. Statistical analysis was performed using Review Manager 5.4. RESULTS: A total of 11 clinical trials met the selection criteria. The pooled analysis' findings demonstrated that both primary and secondary indicators had improved. Compared to the control group, infusion of mesenchymal stem cells significantly increased ALB levels in 2 weeks, 1 month, 3 months, and 6 months, and significantly decreased MELD score in 1 month, 2 months, and 6 months, according to a subgroup analysis using a random-effects model. Additionally, the hepatic arterial injection favored improvements in MELD score and ALB levels. Importantly, none of the included studies indicated any severe adverse effects. CONCLUSION: The results showed that mesenchymal stem cell was effective and safe in the treatment of liver cirrhosis, improving liver function (such as a decrease in MELD score and an increase in ALB levels) in patients with liver cirrhosis and exerting protective effects on complications of liver cirrhosis and the incidence of hepatocellular carcinoma. Although the results of the subgroup analysis were informative for the selection of mesenchymal stem cells for clinical treatment, a large number of high-quality randomized controlled trials validations are still needed.

Design, Synthesis, Antitumour Evaluation, and In Silico Studies of Pyrazolo-[1,5-c]quinazolinone Derivatives Targeting Potential Cyclin-Dependent Kinases.

An efficient, straightforward, and metal-free methodology to rapidly access functionalised pyrazolo-[1,5-c]quinazolinones via a [3 + 2] dipolar cycloaddition and regioselective ring expansion process was developed. The synthesised compounds were characterised by methods such as NMR, HRMS, and HPLC. The in vitro antiproliferative activity against A549 cells (non-small cell lung cancer) was significant for compounds 4i, 4m, and 4n with IC50 values of 17.0, 14.2, and 18.1 µM, respectively. In particular, compounds 4t and 4n showed inhibitory activity against CDK9/2. Predicted biological target and molecular modelling studies suggest that the compound 4t may target CDKs for antitumour effects. The synthesised derivatives were considered to have moderate drug-likeness and sufficient safety in silico. In summary, a series of pyrazolo-[1,5-c]quinazolinone derivatives with antitumour activity is reported for the first time. We provide not only a simple and efficient synthetic method but also helpful lead compounds for the further development of novel cyclin-dependent kinase (CDK) inhibitors.

The value of hematocrit for predicting bronchopulmonary dysplasia in very low birth weight preterm infants.

To determine hematocrit (HCT) and to identify independent risk factors for predicting bronchopulmonary dysplasia (BPD) in preterm infants with very low birth weight (VLBW) infants. This retrospective study included 296 premature infants with VLBW in the neonatal intensive care unit of the First Affiliated Hospital of the University of Science and Technology of China between January 2015 and December 2019. Maternal pregnant information and clinical information as well as hematological parameters of preterm babies were collected and compared. Then the maximum area under the curve of receiver operating characteristic curve was developed to estimate the predictive indicator in the blood. Finally, differential variables together with the predictive index were screened for multiple logistic regression analysis to determine independent prognostic factors for BPD. Infants were divided into a BPD group (134 cases) and a non-BPD group (162 cases). The area under the curve of HCT at postnatal 1 week was 0.737 with the sensitivity of 52.30 % and the specificity of 86.00%. Birth weight (BW) <1.12 kg, gestational age <28.4 weeks, newborn respiratory distress syndrome, mechanical ventilation ≥ 7 days, ventilation associated pneumonia, patent arterial duct, PaO2/FiO2 <300 mm Hg and HCT <0.455 at postnatal 1 week were risk factors for BPD of VLBW infants. HCT levels below 0.455 at 1 week after birth serve as a valuable indicator for the potential development of BPD.

Boron decreases cadmium accumulation in water spinach by enhancing cadmium retention in the root cell walls.

Cadmium (Cd) contamination and boron (B) deficiency are two major challenges associated with the farmland soils in Southern China. Therefore, this study was conducted to examine the impacts of B supply on Cd accumulation in water spinach (Ipomoea aquatica) using a cultivar (T308) with high Cd accumulation. The study further investigated the physiological mechanism behind the changes in Cd accumulation due to B supply. The findings revealed that B supply substantially reduced the Cd concentration in the leaves of water spinach by 41.20% and 37.16% under the Cd stress of 10 µM and 25 µM, respectively. Subcellular distribution of Cd showed that the Cd content as well as its proportion in root cell wall (RCW) increased significantly after B supply. Fourier transform infrared spectroscopy showed significant enrichment of negatively charged groups (such as -OH, -COOH, and -NH2) in the RCW after B supply. Overall, B supply also enhanced covalently bound pectin (CSP) content as well as the Cd content linked with CSP under Cd stress. These observations revealed that B regulated the Cd chelation in RCW, thereby reducing the amassment of Cd in water spinach.

A Potential Anti-Glioblastoma Compound LH20 Induces Apoptosis and Arrest of Human Glioblastoma Cells via CDK4/6 Inhibition.

Glioblastoma (GBM) is a deadly brain tumor characterized by signaling dysregulation and aberrant cell cycle control. The CDK4/6-Rb axis is dysregulated in approximately 80% of all GBM cases. In this study, the anti-GBM effect of a novel pyrimidin-2-amine, LH20 was evaluated in vitro using the primary GBM cell lines U87MG and U251. GBM cells were administered LH20 at concentrations of 0.1, 1, 4, 8, 10, 20, 100, and 200 µM for 24 and 48 h, and the proliferation rate was evaluated using a CCK8 assay. Migration, apoptosis, and cell cycle were also assessed using a wound healing assay, Annexin V-FITC/PI apoptosis assay, and cell cycle staining, respectively. The targets of LH20 were predicted using SwissTargetPrediction and molecular docking. Western blotting analysis was performed to confirm the anti-GBM mechanism of LH20. We found that at concentrations of 4, 8, and 10 µM, LH20 significantly inhibited the proliferation and migration of U87MG and U251 cells, induced late phase apoptosis, promoted tumor cell necrosis, and arrested the G2/M phase of the cell cycle. LH20 also inhibited CDK4 and CDK6 activities by decreasing the phosphorylation of Rb. Our results suggest LH20 as a potential treatment strategy against GBM.

Reduning alleviates sepsis-induced acute lung injury by reducing apoptosis of pulmonary microvascular endothelial cells.

Introduction: Sepsis-induced acute lung injury (SALI) is a critical illness with high mortality, and pulmonary microvascular endothelial cells (PMECs) barrier dysfunction is a well-documented pathogenesis of SALI. The current study aimed to investigate the underlying mechanism of Reduning (RDN) in the treatment of SALI. Methods: Network pharmacology and molecular dynamics simulation (MDS) were used to confirm the possibility of key active components of RDN combining with AKT1. Hematoxylin-eosin staining (HE) and immunohistochemistry (IHC) were used to investigate the effect of RDN in vivo. Immunofluorescence (IF) and co-immunoprecipitation (CoIP) were used to investigate the relationship between mammalian target of rapamycin (mTOR) and Bax in PMECs. ELISA was used to test the level of TNF-α. Flow cytometry was used to detect apoptosis. JC-1 and electron microscopy were used to evaluate mitochondrial damage. The results showed that RDN likely alleviated SALI via targeting AKT1. Results: In vivo, RDN could evidently decrease the expression levels of apoptosis-related proteins, alleviate mitochondrial damage, reduce lung tissue edema, down-regulate the level of TNF-α in the serum, and improve the mortality of sepsis in mice. In vitro, RDN had a significant effect on reducing the level of apoptosis-related proteins and cell apoptosis rate, while also mitigated mitochondrial damage. Furthermore, RDN could effectively lower the level of Bax in PMECs and increase the level of mTOR both in vivo and in vitro. Notably, mTOR has the ability to directly bind to Bax, and RDN can enhance this binding capability. Discussion: RDN could attenuate SALI through reducing apoptosis of PMECs, which is a promising therapeutic strategy for SALI prevention.

A novel suture bridge anchor fixation technique to treat inferior pole fractures of patella: A retrospective clinical study.

The traditional surgical methods to the fracture of the inferior patellar fracture include steel wire tension band fixation and inferior patellar resection, which have many disadvantages. In order to overcome the disadvantages of traditional surgery, we innovated and improved the double row anchor suture bridge technology to the treat the inferior patellar fracture. This study is to investigate the method, technique and clinical efficacy of double-row anchor suture bridge technique in the treatment of inferior pole fractures of patella. Between January 2019 and March 2021, 36 patients with inferior pole fractures of patella underwent the surgery with the double-row anchor suture bridge technique. 28 injury cases were caused by falls while 8 injury cases were from car crashes. The operation time, amount of intraoperative bleeding and complications were recorded. Radiological assessments and Bostman score were performed 1, 3, and 6 months post-operation and at the most recent follow-ups. The study sample consisted of 19 males and 17 females, aged 31 to 72 years old. The operation time was (54-76) minutes. All incisions healed in 1 stage. No complications such as incision infection, flap necrosis and nerve injury occurred. Patients in this group were followed up for 10 to 18 months, with an average follow-up of 12 months. All fractures healed in 10 to 20 weeks, with an average healing time of 12 weeks. At the last follow-up, the Bostman score was (27.5 ± 3.3), excellent in 32 cases and good in 2 cases, with an excellent rate of 94.4%. The range of motion of the knee joint was (-2.6 ± 2.0)° when the knee was extended and (122 ± 5.0)° when the knee was bent. The muscle strength of quadriceps femoris was grade 5. Double-row anchor suture bridge technique is applied to inferior pole fractures of patella by virtue of its various effects, such as the complete preservation of the inferior pole fragments during the operation, satisfactory fracture reduction, firm fixation, and meeting patients' requirements for early postoperative ambulation. In summary, double-row anchor suture bridge technique is an ideal surgical procedure for the treatment of the inferior pole fracture of patella with safety, reliability and high satisfaction.

Auriculotherapy Modulates Macrophage Polarization to Reduce Inflammatory Response in a Rat Model of Acne.

Background: The inflammatory response is an important part of the pathogenesis of acne vulgaris. Auriculotherapy has been shown to have a good therapeutic effect on this disease. The aim of this study was to explore the mechanism underlying the anti-inflammatory effect of auriculotherapy in the treatment of acne vulgaris. Methods: Propionibacterium acnes was injected subcutaneously into the ears of rats to establish an animal model of acne. The auriculotherapy intervention in rats consisted of auricular bloodletting therapy (ABT), auricular point sticking (APS), or a combination of both (ABPS). The anti-inflammatory effects of auriculotherapy were evaluated by measuring changes in ear thickness, local body surface microcirculation in the ear, and serum inflammatory factors in rats. The polarization of macrophages was analyzed by flow cytometry, and the expression of TLR2/NF-κB signaling pathway in the target tissues was analyzed using western blot. Results: ABT, APS, and ABPS all reduced the erythema of ear acne, decreased microcirculation in localized ear acne, and decreased serum levels of TNF-α and IL-1ß in rats. Meanwhile, the three interventions reduced M1-type macrophages and increased M2-type macrophages; only APS could reduce the expression of TLR2/NF-κB signaling pathway. Conclusion: ABT, APS, and ABPS can improve the inflammatory symptoms of acne and reduce inflammatory cytokines. APS may exert anti-inflammatory effects by altering macrophage polarization and decreasing TLR2/NF-κB expression.

Macathioureas A-D, four new thiourea analogues from the roots of Lepidium meyenii.

Macathioureas A-D (1-4), four new thiourea derivatives with a carbamothioylpyrrolidine-2-carboxamide framework, were isolated from the roots of Lepidium meyenii (Maca) collected from Qujing, Yunnan Province of China. Their structures were identified based on extensive spectroscopic data, including 1D NMR, 2D NMR, and HRESIMS techniques. Their absolute configurations were assigned as 7S by the comparison of the experimental and predicted electronic circular dichroism (ECD) spectra. All the thiourea analogues were tested for their cytotoxicities against five human cancer cell lines. However, no significant activities were detected at concentrations up to 40 µM.

Exploration of s new biomarker in osteosarcoma and association with clinical outcomes: TOP2A+ cancer associated fibroblasts.

BACKGROUND: Osteosarcoma (OS) is the leading malignant primary bone tumor in young adults and children and has a high mortality rate. Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment, influencing cancer progression and metastasis. However, there is no systematic study on the role of CAF in OS. METHODS: We collected six OS patients' single-cell RNA sequencing data from the TISCH database, which was processed using the Seurat package. We selected gene sets from the well-known MSigDB database and resorted to the clusterprofiler package for gene set enrichment analysis (GSEA). The least absolute shrinkage and selection operator (LASSO) regression model was used for identification of the variables. Receiver operating characteristic and decision curve analyses were utilized for determining the efficacy of the monogram model. RESULTS: TOP2A+ CAFs was recognized as the carcinogenic CAFs subset, given its intense interaction with OS malignant cells and association with the critical cancer driver pathway. We intersected the differentially expressed genes of TOP2A+ CAFs with the prognostic genes selected from 88 OS samples. The acquired gene set was selected using the LASSO regression model and integrated with clinical factors to obtain a monogram model of high prognosis predicting power (area under the curve of 5 year survival at 0.883). Functional enrichment analysis revealed the detailed difference between two risk groups. CONCLUSION: We identified TOP2A+ CAFs as a subset of oncogenic CAFs in OS. Based on differentially expressed genes derived from TOP2A+ CAFs, combined with bulk transcriptome prognostic genes, we constructed a risk model that can efficiently predict OS prognosis. Collectively, our study may provide new insights for future studies to elucidate the role of CAF in OS.

Ru(II) Complexes with Enaminone Structures for Rapid Sterilization of Staphylococcus aureus and MRSA with Little Accumulation of Drug Resistance.

Drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), pose a serious threat to human life. Therefore, there is urgent need to develop antibiotics with new chemical structures and antibacterial mechanisms, especially those that elicit little drug resistance after long-term use. Herein we synthesized three novel ruthenium complexes (Ru1-Ru3) containing the enaminone structures for the first time. At a concentration of 5 µM, Ru1-Ru3 can lead to a CFU reduction of about 5 log units towards S. aureus and MRSA. Interestingly, Ru3 displayed rapid bactericidal effects and could decrease the CFU numbers of both pathogens by 5 log units within 40 min. The control compounds (Ru4 and Ru5) without the enaminone structures displayed very poor antibacterial activity under the same conditions. Moreover, S. aureus did not show apparent drug resistance towards Ru3 after 20 passages incubation with a sublethal concentration. These results highlight the critical role of enaminone structures for antibacterial applications.